Bioactive peptides in preterm human milk: Impact of maternal characteristics and their association to neonatal outcomes.

Human milk adipokines in term babies seem partially determined by maternal factors and affect infant's development. We aimed to describe bioactive peptide concentration in very preterm human milk and associations to maternal characteristics and postnatal growth. Mothers delivering ≤32 weeks of gestation and their infant/s were recruited. At 4 weeks of lactation, an aliquot of 24-h-pooled milk was collected for exclusively breastfeeding dyads. Insulin, leptin, adiponectin, and milk fat globule epidermal growth factor-8 (MFG-E8) were measured by enzyme-linked immunoabsorbent assay in skimmed milk. One hundred mothers (28.8 ± 2.3 weeks at delivery) provided a milk sample. Milk insulin was related to gestational age, pre-pregnancy body mass index (BMI), and galactagogue treatment (final model: adjusted R2 : 0.330, p < 0.0001; adjusted ß coefficients: galactagogue treatment: 0.348, p 0.001; pre-pregnancy BMI: 0.274, p 0.009; gestational age: -0.290, p 0.007). Adiponectin was higher in mothers with gestational diabetes (30.7 ± 6.5 vs. 24.8 ± 8 ng/mL, p 0.044). Leptin was associated with pre-pregnancy BMI (Spearman's ρ: 0.648, p < 0.0001) and MFG-E8 to presence of labor and multiple pregnancy (final linear regression model, R2 : 0.073, p 0.028, adjusted ß coefficients: presence of labor -0.229, p 0.050; twins: -0.192, p 0.099). Milk adiponectin was associated with a greater decrease in length z-scores from birth to 28 days (Pearson's r: -0.225, p 0.032) and to discharge (Pearson's r: -0.290, p 0.003). Milk MFG-E8 was lower in milk of mothers whose babies experienced late-onset sepsis (13.3 ± 5.8 vs. 16.8 ± 6.3 µg/mL, p 0.023). Adipokines levels in preterm human milk are partially related to maternal metabolic status. Milk peptide concentration associates with early neonatal growth trajectories.

Influence of maternal and perinatal factors on macronutrient content of very preterm human milk during the first weeks after birth.

OBJECTIVE: To identify changes in macronutrient content of very preterm human milk associated with perinatal factors. STUDY DESIGN: Milk macronutrients were measured on weeks 1, 2, 4 and 8 with mid-infrared transmission spectrometers. RESULT: We assessed 625 samples (from 117 mothers and 130 very preterm infants). Average concentrations were: protein 1.3 ± 0.3 g/dl, carbohydrates 7.3 ± 0.6 g/dl, fat 3.7 ± 1.0 g/dl and energy 296.0 ± 41.0 kJ/dl (70.7 kcal/dl). Gestational age negatively correlated with protein (rho: -0.307, p < 0.001) and energy (r: -0.193, p = 0.003). Advanced maternal age, gestational age and intrauterine growth restriction were independently associated with milk protein content over the first 4 weeks (adjusted R2: 0.113, p = 0.002). CONCLUSION: These findings may help neonatologists identify patients fed Mother´s Own Milk who are at increased risk of poor postnatal growth.

Lung ultrasound for early surfactant treatment: Development and validation of a predictive model.

AIM: To develop and validate a feasible predictive model for early surfactant treatment in very preterm infants (VPI) admitted with respiratory distress syndrome (RDS). METHODS: Preterm infants less than 32 weeks of gestation with RDS and stabilized with noninvasive ventilation in delivery room were recruited (January 2018-April 2020). Clinical data, chest X-ray (CXR) score, respiratory support, oxygen saturation/fraction of inspired oxygen ratio (SF ratio), lung ultrasound (LUS) score, and diaphragmatic thickening fraction (DTF) were recorded at 60-120 min of life. Oxygen threshold for surfactant administration was fraction of inspired oxygen more than 30%; ultrasound findings were blinded. Logistic regression models using a stepwise selection of variables were developed in the derivation cohort. Coefficients from these models were applied to the validation cohort and a diagnostic performance was calculated. RESULTS: A total of 144 VPI with a mean gestational age of 28.7 ± 2.2 weeks were included (94 into the derivation cohort, 50 into the validation cohort); 37 required surfactant treatment (25.7%). Gestational age, SF ratio, LUS score, CXR score, and Silverman score were related to surfactant administration (R2 = .823). Predictors included in the final model for surfactant administration were SF ratio and LUS score (R2 = .783) with an area under the receiver operating characteristic (AUC) = 0.97 (95% confidence interval [CI]: 0.93-1.00) in the derivation cohort and an AUC = 0.95 (95% CI: 0.85-0.99) in the validation cohort. By applying our predictive model, 26 patients (70.2%) would have been treated with surfactant earlier than 2 h of life. CONCLUSION: The predictive model showed a high diagnostic performance and could be of value to optimize early respiratory management in VPI with RDS.

Reply: "It is Time for a Universal Nutrition Policy in Very Preterm Neonates during the Neonatal Period? Comment on: Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants Nutrients 2019, 11, 2772".

We would like to thank Gounaris et al [...].

Infrared analyzers for the measurement of breastmilk macronutrient content in the clinical setting.

INTRODUCTION: There is growing interest in the possibility of measuring the macronutrient content of human milk. Several studies that intend to validate commercially available human milk analyzers have been published with inconsistent results. This review will focus on currently available, verified methodologies for analyzing macronutrients in human milk. AREAS COVERED: A literature search was conducted in the PubMed database. Five milk analyzers were chosen to be included in this review: MIRIS (Uppsala, Sweden) (seven articles found), Calais (Cleveland, United States) (four articles), SpectraStar (Brookfield, United States) (four articles), MilkoScan (Hillerdo, Denmark) (two articles), and Delta LactoScope (Stockholm, Sweden) (one article). The following information was extracted from published manuscripts: measuring device, sample preparation, purpose of the study, type of macronutrients studied, results, and conclusions. EXPERT OPINION: Infrared spectroscopy can be an accurate and reliable technology for assessing the macronutrient content of human milk, specifically crude protein, and total fat. However, an optimal handling of samples, the development of standardized quality-control protocols, and an improvement in calibration procedures are required before the full implementation of infrared technology in neonatal units.

Plasma Metabolome Alterations Associated with Extrauterine Growth Restriction.

Very preterm infants (VPI, born at or before 32 weeks of gestation) are at risk of adverse health outcomes, from which they might be partially protected with appropriate postnatal nutrition and growth. Metabolic processes or biochemical markers associated to extrauterine growth restriction (EUGR) have not been identified. We applied untargeted metabolomics to plasma samples of VPI with adequate weight for gestational age at birth and with different growth trajectories (29 well-grown, 22 EUGR) at the time of hospital discharge. A multivariate analysis showed significantly higher levels of amino-acids in well-grown patients. Other metabolites were also identified as statistically significant in the comparison between groups. Relevant differences (with corrections for multiple comparison) were found in levels of glycerophospholipids, sphingolipids and other lipids. Levels of many of the biochemical species decreased progressively as the level of growth restriction increased in severity. In conclusion, an untargeted metabolomic approach uncovered previously unknown differences in the levels of a range of plasma metabolites between well grown and EUGR infants at the time of discharge. Our findings open speculation about pathways involved in growth failure in preterm infants and the long-term relevance of this metabolic differences, as well as helping in the definition of potential biomarkers.

Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants.

AIM: To analyze different methods to assess postnatal growth in a cohort of very premature infants (VPI) in a clinical setting and identify potential early markers of growth failure. METHODS: Study of growth determinants in VPI (≤32 weeks) during hospital stay. Nutritional intakes and clinical evolution were recorded. Growth velocity (GV: g/kg/day), extrauterine growth restriction (%) (EUGR: weight < 10th centile, z-score < -1.28) and postnatal growth failure (PGF: fall in z-score > 1.34) at 36 weeks postmenstrual age (PMA) were calculated. Associations between growth and clinical or nutritional variables were explored (linear and logistic regression). RESULTS: Sample: 197 VPI. GV in IUGR patients was higher than in non-IUGRs (28 days of life and discharge). At 36 weeks PMA 66.0% of VPIs, including all but one of the IUGR patients, were EUGR. Prevalence of PGF at the same time was 67.4% (IUGR patients: 48.1%; non-IUGRs: 70.5% (p = 0.022)). Variables related to PGF at 36 weeks PMA were initial weight loss (%), need for oxygen and lower parenteral lipids in the first week. CONCLUSIONS: The analysis of z-scores was better suited to identify postnatal growth faltering. PGF could be reduced by minimising initial weight loss and assuring adequate nutrition in patients at risk.